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A Study of Selinexor in Combination With Azacitidine and Venetoclax (SAV Regimen) in Treatment Naïve Participants With Acute Myeloid Leukemia

Phase 2
Recruiting
Conditions
AML, Adult
Interventions
Registration Number
NCT05736965
Lead Sponsor
Shanghai Tong Ren Hospital
Brief Summary

This is a prospective, single-arm, multi-center clinical trial to evaluate the efficacy and safety of selinexor in combination with azacitidine and venetoclax for untreated acute myeloid leukemia.

Detailed Description

This is a prospective, single-arm, multi-center clinical trial to evaluate the efficacy and safety of selinexor in combination with azacitidine and venetoclax for untreated acute myeloid leukemia.

Selinexor will be given orally at 60mg, d3,10,17 Azacitidine will be given at 75mg/m2, d1-3, 8-9, 15-16 Venetoclax will be given orally at 100mg on day 1 and 200mg on day 2, 400mg on day 3-14

28 days per cycle, patients can receive transplants at any time once they achieved complete remission and other patients will continue to receive treatment until disease progression or unacceptable toxic effects.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
58
Inclusion Criteria
  • Known and written informed consent voluntarily

  • Age ≥ 18 years

  • Newly diagnosed AML patients (per WHO 2022 classification criteria for AML diagnosis), who are not suitable for intensive chemotherapy:

    • ≥75 years or
    • Aged 18 to 74 years with at least one of the following comorbidities: Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or 3 or 4; Cardiac history of Congestive Heart Failure (CHF) requiring treatment or Ejection Fraction <= 50% or chronic stable angina; Diffusing capacity of the Lung for Carbon Monoxide (DLCO) <= 65% or Forced Expiratory Volume in 1 second (FEV1) <= 65%; Creatinine clearance >= 30 mL/min to < 45 ml/min; Moderate hepatic impairment with total bilirubin > 1.5 to <= 3.0 × Upper Limit of Normal (ULN); Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy .
  • patients who are suitable for intensive chemotherapy but refuse it

  • Liver function meets the following criteria:

aspartate aminotransferase (AST) ≤ 3.0×ULN*; alanine aminotransferase (ALT) ≤ 3.0×ULN*; Bilirubin≤1.5×ULN*; For subjects <75 years old, the bilirubin level can be ≤3.0×ULN;

  • Unless due to leukemic organ involvement.

    • Renal function meets the following criteria: creatinine clearance ≥ 30 mL/min (Cockroft-Gault formula)
    • Life expectancy ≥ 4 weeks
Exclusion Criteria
  • History of any malignancies prior to study entry with exception noted in the protocol.
  • Participant has known HIV infection, active hepatitis B virus (HBV) and/or hepatitis C virus (HCV) .
  • Participant has known active central nervous system (CNS) involvement with AML.
  • Must not have received prior anti-AML treatment except for hydroxyurea

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
SAV armSelinexorUntreated acute myeloid leukemia who are ineligible for intensive chemotherapy or who refuse to receive intensive chemotherapy will receive selinexor in combination with azacitidine and venetoclax, 28 days per cycle, patients can receive transplants at any time once they achieved complete remission and other patients will continue to receive SAV regimen until disease progression or unacceptable toxic effects.
SAV armVenetoclaxUntreated acute myeloid leukemia who are ineligible for intensive chemotherapy or who refuse to receive intensive chemotherapy will receive selinexor in combination with azacitidine and venetoclax, 28 days per cycle, patients can receive transplants at any time once they achieved complete remission and other patients will continue to receive SAV regimen until disease progression or unacceptable toxic effects.
SAV armAzacitidineUntreated acute myeloid leukemia who are ineligible for intensive chemotherapy or who refuse to receive intensive chemotherapy will receive selinexor in combination with azacitidine and venetoclax, 28 days per cycle, patients can receive transplants at any time once they achieved complete remission and other patients will continue to receive SAV regimen until disease progression or unacceptable toxic effects.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Composite Complete RemissionFrom the study start up to death (up to approximately 2 years; )

composite complete remission(CR , CRh, CRi) was calculated based on ELN2022 criteria.

Secondary Outcome Measures
NameTimeMethod
Overall response rate(ORR)From the study start up to death (up to approximately 4 years; )
Recurrence Free Survival(RFS)From the study start up to death (up to approximately 4 years; )
overall survival (OS)From the study start up to death (up to approximately 4 years; )
percentage of patients who achieved MRD negativityFrom the study start up to death (up to approximately 4 years; )

Trial Locations

Locations (19)

Jilin University China Japan Union Hospital

🇨🇳

Ch'ang-ch'un, China

Changzhou Municipal No.1 People's Hospital

🇨🇳

Changzhou, China

Sichuan Provincial People's Hospital

🇨🇳

Chengdu, China

Harbin Institute of Hematology and Oncology

🇨🇳

Ha'erbin, China

Gansu Provincial People's Hospital

🇨🇳

Lanzhou, China

Anhui Provincial Hospital

🇨🇳

Hefei, China

the first hospital of Jiaxing affiliated hospital of Jiaxing University

🇨🇳

Jiaxing, China

Lanzhou University NO.2 Hospital

🇨🇳

Lanzhou, China

Ningbo Medical Center Lihuili Huspital

🇨🇳

Ningbo, China

Shanghai Ruijin Hospital

🇨🇳

Shanghai, China

Shanghai Tong Ren hospital

🇨🇳

Shanghai, China

Yixing People's Hospital

🇨🇳

Yixing, China

The First Hospital of Hebei Medical University

🇨🇳

Shijia Zhuang, China

The Second Hospital of Hebei Medical University

🇨🇳

Shijia Zhuang, China

The First Hospital of China Medical University

🇨🇳

Shenyang, China

Xi'an International Medical Center

🇨🇳

Xi'an, China

Northern Jiangsu People's Hospital

🇨🇳

Yangzhou, China

the Second Affiliated Hospital of Wannan Medical College

🇨🇳

Wuhu, China

First Affiliated Hospital of Xinjiang Medical University

🇨🇳

Ürümqi, China

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